The uterus is a unique mucosal organ because it must not only cope with the hazards of exposure to the external environment, but it must serve as the recipient site in the natural transplantation of genetically alien spermatozoa and conceptuses that is required for mammalian reproduction. Since females do not usually mount harmful immune responses to these cells and tissues, it seems likely that the "graft site" is uniquely designed to allow such exposures and that it plays a key role in insuring that maternal immune recognition results in protective, not destructive, effectors. The long-term goals of this application are to elucidate how foreign substances are processed in the uterus and subsequently exposed to the host's lymphoid system and the immunologic consequences. The specific aims encompass three groups of studies bearing on these goals. Firstly, the major study will be a careful morphological assessment of the lymphatic vessels of the rat endometrium using perfusion fixation which allows even small lymphatics to be visualized by both light and electron microscopy. The distribution of lymphatics in virgin and early pregnancy uteri and their relationship to the implant site and decidual capsule will be determined. Three-dimensional images will be generated by computer reconstruction. Comparative studies will be performed on uteri from several species with widely varying types of implantation and placentation. Secondly, the distribution and density of Ia+ (potential antigen-presenting) cells in both virgin and pregnancy uteri will be assessed, using indirect immunofluorescence and monoclonal antibodies. We will also determine the ontogenetic appearance of these cells and possible hormonal influences on their distribution. Thirdly, how natural antigens, spermatozoa, are handled in the uterus will be studied by tracing sperm labeled with fluorescent tags and comparing with similar assessments of sperm placed in the intestine, a different mucosa with distinct lymphoid structures and epithelial cells designed for antigen uptake. Sperm will be placed in the rectum and in modified Thiry-Vella ileal loops with and without Peyer's patches. Because exposures to sperm via this route could be related to acquired immune deficiency syndrome among homosexual males, the effect of multiple sperm exposures on host immuno-competence and production of antisperm antibodies will be compared with that in females exposed by the natural route.